Antibiotics

18 pages, 786 KiB

Open AccessArticle

Prevalence and Associated Mortality of Infections by Multidrug-Resistant Organisms in Pediatric Intensive Care Units in Argentina (PREV-AR-P)

by Wanda Cornistein, Carina Balasini, Yanina Nuccetelli, Viviana M. Rodriguez, Norma Cudmani, Maria Virginia Roca, Graciela Sadino, Martín Brizuela, Analía Fernández, Soledad González, Damián Águila, Alejandra Macchi, Maria Inés Staneloni and Elisa Estenssoro

Antibiotics 2025, 14(5), 493; https://doi.org/10.3390/antibiotics14050493 (registering DOI) - 11 May 2025

Abstract

Background/Objectives: Data on multidrug-resistant organism (MDRO) infections in children are scarce, especially in resource-limited regions. This study aimed to estimate the prevalence of MDRO infections in pediatric intensive care units (PICUs) and characterize their epidemiologic and clinical features. Methods: A national, multicenter, point-prevalence [...] Read more.

Background/Objectives: Data on multidrug-resistant organism (MDRO) infections in children are scarce, especially in resource-limited regions. This study aimed to estimate the prevalence of MDRO infections in pediatric intensive care units (PICUs) and characterize their epidemiologic and clinical features. Methods: A national, multicenter, point-prevalence study was conducted in 50 PICUs in Argentina over 24 h between 24 and 28 November 2023. The primary study outcome was the prevalence of ICU infections caused by MDROs. Secondary outcomes included the prevalence of carbapenemase-producing Enterobacterales (CPE) colonization, ICU mortality, and ICU length of stay (LOS_ICU). Results: 304 patients were included. The overall prevalence of infection was 45.1% (137/304); of these, 50.3% (69/137) were hospital-acquired. Among the 137 patients with reported infections, 49.6% (n = 68) were classified as definite (microbiologically confirmed) and 50.4% (n = 69) as probable (no confirmatory microbiology). Among definite infections, 20.6% (n = 14) were due to MDROs. The overall prevalence of MDRO infections was 4.6% (14/304). Extended-spectrum β-lactamase (ESBL)-producing organisms were the most commonly identified microorganisms (42.9%), followed by CPE (28.6%). Ventilator-associated pneumonia (VAP) was the most frequent location of MDRO infections. The prevalence of CPE colonization was 13.2%. Mortality was low (5.3%) and similar in patients with MDRO and non-MDRO infections. LOS_ICU was longer in patients with MDRO infections compared to patients with non-MDRO infections (81 [22–150] vs. 25 [12–27] days, respectively, p = 0.0007). Conclusions: Among 304 PICU patients, the prevalence of MDRO infections and colonization was relatively low. MDRO infections were not associated with increased mortality but were associated with longer ICU stays, compared to patients with non-MDRO infections. Full article

(This article belongs to the Special Issue Nosocomial Infections and Complications in ICU Settings)

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15 pages, 7498 KiB

Open AccessArticle

Lack of Spontaneous and Adaptive Resistance Development in Staphylococcus aureus Against the Antimicrobial Peptide LTX-109

by Bhupender Singh, Mia Angelique Winkler, Wasifa Kabir, Johanna U Ericson and Arnfinn Sundsfjord

Antibiotics 2025, 14(5), 492; https://doi.org/10.3390/antibiotics14050492 (registering DOI) - 11 May 2025

Abstract

Nasal carriage of Staphylococcus aureus and its antibiotic-resistant derivative, methicillin-resistant S. aureus (MRSA), is a risk factor for nosocomial S. aureus infections. Mupirocin is a topical antibiotic and a key in the decolonization of both methicillin-susceptible S. aureus (MSSA) and MRSA carriage in [...] Read more.

Nasal carriage of Staphylococcus aureus and its antibiotic-resistant derivative, methicillin-resistant S. aureus (MRSA), is a risk factor for nosocomial S. aureus infections. Mupirocin is a topical antibiotic and a key in the decolonization of both methicillin-susceptible S. aureus (MSSA) and MRSA carriage in patients and health care personnel. Recent observations have shown a global increase in the prevalence of mupirocin-resistant MSSA and MRSA, reducing the efficacy of mupirocin in decolonization regimens. LTX-109 is a peptidomimetic synthetic compound that has shown broad-spectrum bactericidal antimicrobial activity in vitro and in animal experiments. However, the development of resistance against LTX-109 in clinical isolates of MRSA and MSSA has not been systematically examined. Background/Objectives: Here, we assess the development of spontaneous and adaptive resistance against LTX-109 in genomically diverse MRSA (n = 3) and MSSA (n = 4) strains. Methods: Adaptive and mutational resistance were examined by serial passaging strains over 60 cycles in a range of LTX-109 and mupirocin concentrations. Spontaneous resistance was examined in high-inoculum agar plates with 2–8 times the concentration above MIC. Results: Throughout serial passage, LTX-109 MICs varied less than 4-fold compared to the initial MIC of 4–8 mg/L, while mupirocin MICs increased in all susceptible strains (n = 5) from 0.25 mg/L to 16–512 mg/L. The spontaneous resistance assay demonstrated no resistance development at 4–8× MIC LTX-109 and an inoculum effect at 2× MIC. Conclusions: Our results demonstrate the novelty of LTX-109 as an antimicrobial agent with no detectable in vitro resistance development in selected clinical strains of MRSA and MSSA. Full article

(This article belongs to the Special Issue Strategies for Combatting Multidrug-Resistant and Extensively Drug-Resistant Bacteria, 2nd Edition)

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18 pages, 3148 KiB

Open AccessArticle

Antimicrobial Susceptibility Profiles of Escherichia coli Isolates from Clinical Cases of Ducks in Hungary Between 2022 and 2023

by Ádám Kerek, Ábel Szabó and Ákos Jerzsele

Antibiotics 2025, 14(5), 491; https://doi.org/10.3390/antibiotics14050491 (registering DOI) - 10 May 2025

Abstract

Background: Antimicrobial resistance (AMR) poses a growing threat to veterinary medicine and food safety. This study examines Escherichia coli antibiotic resistance patterns in ducks, focusing on multidrug-resistant (MDR) strains. Understanding resistance patterns and predicting MDR occurrence are critical for effective intervention strategies. [...] Read more.

Background: Antimicrobial resistance (AMR) poses a growing threat to veterinary medicine and food safety. This study examines Escherichia coli antibiotic resistance patterns in ducks, focusing on multidrug-resistant (MDR) strains. Understanding resistance patterns and predicting MDR occurrence are critical for effective intervention strategies. Methods: E. coli isolates were collected from duck samples across multiple regions. Descriptive statistics and resistance frequency analyses were conducted. A decision tree classifier and a neural network were trained to predict MDR status. Cross-resistance relationships were visualized using graph-based models, and Monte Carlo simulations estimated MDR prevalence variations. Results: Monte Carlo simulations estimated an average MDR prevalence of 79.6% (95% CI: 73.1–86.1%). Key predictors in MDR classification models were enrofloxacin, neomycin, amoxicillin, and florfenicol. Strong cross-resistance associations were detected between neomycin and spectinomycin, as well as amoxicillin and doxycycline. Conclusions: The high prevalence of MDR strains underscores the urgent need to revise antibiotic usage guidelines in veterinary settings. The effectiveness of predictive models suggests that machine learning tools can aid in the early detection of MDR, contributing to the optimization of treatment strategies and the mitigation of resistance spread. The alarming MDR prevalence in E. coli isolates from ducks reinforces the importance of targeted surveillance and antimicrobial stewardship. Predictive models, including decision trees and neural networks, provide valuable insights into resistance trends, while Monte Carlo simulations further validate these findings, emphasizing the need for proactive antimicrobial management. Full article

(This article belongs to the Section Antibiotics in Animal Health)

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10 pages, 767 KiB

Open AccessArticle

Prevalence of Acinetobacter baumannii Multidrug Resistance in University Hospital Environment

by Francesco Foglia, Annalisa Ambrosino, Shahab Bashir, Emiliana Finamore, Carla Zannella, Giovanna Donnarumma, Anna De Filippis and Massimiliano Galdiero

Antibiotics 2025, 14(5), 490; https://doi.org/10.3390/antibiotics14050490 (registering DOI) - 10 May 2025

Abstract

Background: Acinetobacter baumannii is a significant pathogen and a major contributor to healthcare-associated infections, particularly in intensive care units. Its high potential for developing multiple drug resistance (MDR) makes it a challenging pathogen to manage. This study investigates the prevalence and resistance [...] Read more.

Background: Acinetobacter baumannii is a significant pathogen and a major contributor to healthcare-associated infections, particularly in intensive care units. Its high potential for developing multiple drug resistance (MDR) makes it a challenging pathogen to manage. This study investigates the prevalence and resistance patterns of MDR A. baumannii isolates over a six-year period at a university hospital in Southern Italy. Objective: The aims of this study are to evaluate recent trends in the prevalence of MDR A. baumannii, analyze resistance patterns, and assess the impact of the antimicrobial diagnostic stewardship program implemented in 2018. Methods: This retrospective cohort study was conducted at the University Hospital of Campania “Luigi Vanvitelli” from 2018 to 2023. A total of 191 A. baumannii isolates from blood, urine, and wound samples were analyzed. Antimicrobial susceptibility testing was performed following EUCAST guidelines. The prevalence of MDR strains was assessed across three periods: pre-pandemic (2018–2019), during the pandemic (2020–2021), and post-pandemic (2022–2023) Results: Among the 191 isolates, 89.5% were classified as MDR. The highest number of isolates occurred in 2020, with blood cultures and urine samples increasing by 40.9% and 62.5%, respectively, while wound isolates decreased by 34.2%. The implementation of antimicrobial diagnostic stewardship programs correlated with a reduction in carbapenem resistance in 2020 and 2022. However, resistance to meropenem and colistin persisted. A 60.4% decline in total isolation from 2020 to 2023 suggests effective infection control measures. Conclusions: MDR A. baumannii remains a significant threat to healthcare. Although there have been slight reductions in resistance following antimicrobial stewardship interventions, persistent resistance to last-line antibiotics underscores the urgent need for alternative treatments, enhanced surveillance, and stricter infection control strategies. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Virulence Mechanisms in Gram-Negative Bacteria: An Alliance for Success)

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23 pages, 3364 KiB

Open AccessArticle

Antimicrobial Resistance and Phylogenetic Analysis of Multidrug-Resistant Non-Typhoidal Salmonella Isolates from Different Sources in Southern Vietnam

by Daria Starkova, Svetlana Egorova, Ludmila Suzhaeva, Truong Quang Nguyen, Lidiia Kaftyreva, Maria Makarova, Samida Zhamborova, Dmitrii Polev, Alina Saitova, Vu Hoang Nguyen, Tram Khac Vo and Long Thanh Nguyen

Antibiotics 2025, 14(5), 489; https://doi.org/10.3390/antibiotics14050489 (registering DOI) - 10 May 2025

Abstract

Background/Objectives: Non-typhoidal Salmonella (NTS) is one of the most common causative agents of food poisoning in Vietnam, and contaminated livestock meat poses a major risk to human health. The present study aims to provide the genetic characteristics of NTS with a particular focus [...] Read more.

Background/Objectives: Non-typhoidal Salmonella (NTS) is one of the most common causative agents of food poisoning in Vietnam, and contaminated livestock meat poses a major risk to human health. The present study aims to provide the genetic characteristics of NTS with a particular focus on antimicrobial resistance and determine phylogenetic relationships between isolates from different sources in Southern Vietnam based on whole-genome sequencing (WGS) data. Methods: A total of 49 NTS isolates from pork/broiler meat, pigs, chickens, and humans were collected in Ho Chi Minh City and four provinces of Southern Vietnam. Phenotypic antimicrobial susceptibility testing (AST) and WGS for all isolates were performed. Results: As a result, 14 different serotypes were identified, among which S. Typhimurium and its monophasic variant were the dominant serotypes for human and pig sources. All chicken samples belonged to S. Indiana, whereas S. Infantis predominated in broiler meat. AST results revealed that 98% of isolates were multidrug resistant. NTS strains isolated from poultry and pigs exhibited resistance to the highest priority antimicrobials—quinolones and polymyxin, as well as to β-lactams, aminoglycosides, tetracycline, and sulfonamide, which are considered to be critical for the treatment of severe diseases. Conclusions: The results highlight the utmost importance of issues related to the selection, spreading, and transmission of multi-resistant strains from animals to humans. Full article

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25 pages, 2650 KiB

Open AccessArticle

The Impact of Human Milk Oligosaccharides on Antibiotic-Induced Microbial Dysbiosis and Gut Inflammation in Mice

by Kristine Rothaus Christensen, Torben Sølbeck Rasmussen, Caroline M. Junker Mentzel, Sofie Kaas Lanng, Elena Tina Gabriella Meloni, Hanne Christine Bertram, Camilla Hartmann Friis Hansen and Axel Kornerup Hansen

Antibiotics 2025, 14(5), 488; https://doi.org/10.3390/antibiotics14050488 (registering DOI) - 10 May 2025

Abstract

Background/Objectives: Antibiotics have a significant impact on the gut microbiota, and we hypothesized that human milk oligosaccharides may alleviate antibiotic-induced gut microbiota dysbiosis. Methods: Six groups of eight mice were administered drinking water with or without ampicillin for one week. We [...] Read more.

Background/Objectives: Antibiotics have a significant impact on the gut microbiota, and we hypothesized that human milk oligosaccharides may alleviate antibiotic-induced gut microbiota dysbiosis. Methods: Six groups of eight mice were administered drinking water with or without ampicillin for one week. We then introduced the human milk oligosaccharide 2′-fucosyllactose (2′FL), either alone or in combination with difucosyl-lactose (DFL), for two weeks after the termination of ampicillin treatment. Results: Ampicillin reduced microbiota diversity and the abundance of specific bacteria. One week after the termination of ampicillin treatment, the 2′FL + DFL mixture counteracted the ampicillin-induced reduction in diversity, although this effect was not sustained. Over the subsequent two weeks, the 2′FL + DFL mixture had a significant impact on the relative abundances of Lactobacillus spp. and Bacteroides spp. Ampicillin also reduced caecal propionate levels, downregulated the gene Gzmb for Granzyme B, and upregulated the gene Reg3a for Regenerating islet-derived protein 3 alpha, all of which were counteracted by the 2′FL + DFL mixture. Ampicillin had a minor impact on ileal cytokine levels. The 2′FL + DFL mixture showed a cytokine effect indicating reduced adaptive and innate inflammation. Ampicillin reduced water intake and growth in the mice. The oligosaccharides did not affect water intake, but the 2′FL + DFL mixture slightly reduced body weight. Conclusions: The 2′FL + DFL mixture appears to hold potential for counteracting some of the side effects of ampicillin treatment. Full article

10 pages, 556 KiB

Open AccessPerspective

Virological and Pharmaceutical Properties of Clinically Relevant Phages

by Antonios-Periklis Panagiotopoulos, Antonia P. Sagona, Deny Tsakri, Stefanos Ferous, Cleo Anastassopoulou and Athanasios Tsakris

Antibiotics 2025, 14(5), 487; https://doi.org/10.3390/antibiotics14050487 (registering DOI) - 10 May 2025

Abstract

As antimicrobial resistance continues to undermine the efficacy of antibiotics, the global medical community is increasingly turning to alternative treatment modalities. Among these, phage therapy has re-emerged as a promising strategy for managing multidrug-resistant bacterial infections. Herein, we present and briefly discuss eight [...] Read more.

As antimicrobial resistance continues to undermine the efficacy of antibiotics, the global medical community is increasingly turning to alternative treatment modalities. Among these, phage therapy has re-emerged as a promising strategy for managing multidrug-resistant bacterial infections. Herein, we present and briefly discuss eight essential attributes of clinically relevant phages for therapy, which may be categorized broadly into virological and pharmacological characteristics. Virological attributes include a broad host range, a strictly lytic life cycle and the ability to manage the emergence of bacterial resistance to phages. Comprehensive genomic and proteomic characterization forms the foundation for selecting and engineering such candidates, ensuring both safety and predictability. From a pharmacological standpoint, phages should ideally show safety across relevant formulations and routes of administration, favorable pharmacokinetics, stability during storage and scalability in manufacturing. Advances in genomic analysis, artificial intelligence-driven phage selection and formulation technologies have further accelerated the translational potential of phage therapy. By systematically addressing each of these critical attributes, this work aims to inform the rational selection and development of therapeutic phages suitable for integration into the clinical practice. Full article

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15 pages, 1311 KiB

Open AccessArticle

In Vitro Activity of Imipenem/Relebactam Alone and in Combination Against Cystic Fibrosis Isolates of Mycobacterium abscessus

by Madeline Sanders, Sun Woo Kim, Aditi Shinde, Danielle Fletcher-Williams, Eric Quach and Paul Beringer

Antibiotics 2025, 14(5), 486; https://doi.org/10.3390/antibiotics14050486 (registering DOI) - 10 May 2025

Abstract

Background: Mycobacterium abscessus (MABS) is an opportunistic pathogen that causes chronic, difficult-to-treat pulmonary infections, particularly in people with cystic fibrosis (PwCF), leading to rapid lung function decline and increased morbidity and mortality. Treatment is particularly challenging due to the pathogen’s resistance mechanisms and [...] Read more.

Background: Mycobacterium abscessus (MABS) is an opportunistic pathogen that causes chronic, difficult-to-treat pulmonary infections, particularly in people with cystic fibrosis (PwCF), leading to rapid lung function decline and increased morbidity and mortality. Treatment is particularly challenging due to the pathogen’s resistance mechanisms and the need for prolonged multidrug therapy, which is characterized by poor clinical outcomes and highlights the urgent need for novel therapeutic strategies. Imipenem/relebactam, a novel β-lactam-β-lactamase inhibitor combination, demonstrates in vitro activity against resistant MABS strains and effective pulmonary penetration. Prior research indicates synergistic activity of imipenem with various antibiotics against M. abscessus. Objectives: This study aims to evaluate the in vitro activity of imipenem/relebactam, alone and in combination with various antibiotics, against MABS clinical isolates from PwCF (n = 28). Methods: Susceptibility and synergy were assessed using broth microdilution and checkerboard assays. Extracellular time-kill assays were performed to evaluate the bactericidal activity of synergistic three-drug combinations containing imipenem/relebactam. Results: Imipenem/relebactam demonstrated potent in vitro activity against clinical MABS isolates, exhibiting substantial synergy with cefuroxime, cefdinir, amoxicillin, and cefoxitin. Rifabutin, azithromycin, moxifloxacin, clofazimine, and minocycline also demonstrated additive effects with imipenem/relebactam. Extracellular time-kill assays identified imipenem/relebactam + cefoxitin + rifabutin and imipenem/relebactam + cefoxitin + moxifloxacin as the most effective combinations. Conclusions: These findings suggest that imipenem/relebactam may offer a significant advancement in the management of MABS infections in PwCF. The promising efficacy of multidrug regimens combining imipenem/relebactam with agents like cefoxitin, azithromycin, moxifloxacin, clofazimine, and rifabutin highlights potential therapeutic strategies. Full article

(This article belongs to the Special Issue Antimicrobial Prescribing, Population Use and Resistance, Impact in Global Health, 2nd Edition)

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25 pages, 559 KiB

Open AccessArticle

Phenotypic and Genotypic Characterization of ESBL-, AmpC-, and Carbapenemase-Producing Klebsiella pneumoniae and High-Risk Escherichia coli CC131, with the First Report of ST1193 as a Causative Agent of Urinary Tract Infections in Human Patients in Algeria

by Hajer Ziadi, Fadela Chougrani, Abderrahim Cheriguene, Leticia Carballeira, Vanesa García and Azucena Mora

Antibiotics 2025, 14(5), 485; https://doi.org/10.3390/antibiotics14050485 - 9 May 2025

Abstract

Background: High-risk Escherichia coli clones, such as sequence type (ST)131 and ST1193, along with multidrug-resistant (MDR) Klebsiella pneumoniae, are globally recognized for their significant role in urinary tract infections (UTIs). This study aimed to provide an overview of the virulence factors, clonal [...] Read more.

Background: High-risk Escherichia coli clones, such as sequence type (ST)131 and ST1193, along with multidrug-resistant (MDR) Klebsiella pneumoniae, are globally recognized for their significant role in urinary tract infections (UTIs). This study aimed to provide an overview of the virulence factors, clonal diversity, and antibiotic resistance profiles of extended-spectrum cephalosporin (ESC)-E. coli and K. pneumoniae causing UTIs in humans in the Tebessa region of Algeria. Methods: Forty E. coli and 17 K. pneumoniae isolates exhibiting ESC-resistance were recovered (July 2022–January 2024) from urine samples of patients at three healthcare facilities to be phenotypically and genotypically characterized. Whole genome sequencing (WGS) was performed on the ST1193 clone. Results: Among K. pneumoniae isolates, all except one harbored CTX-M-15, with a single isolate carrying bla_CTX-M-194. Additionally, two K. pneumoniae isolates co-harboring bla_CTX-M-15 and bla_NDM exhibited phenotypic and genotypic hypervirulence traits. Fluoroquinolone resistance (FQR) was detected in 94.1% of K. pneumoniae isolates. The E. coli isolates carried diverse ESC-resistance genes, including CTX-M-15 (87.5%), CTX-M-27 (5%), CTX-M-1, CMY-59, and CMY-166 (2.5% each). Co-carriage of bla_ESCand bla_OXA-48was identified in three E. coli isolates, while 62.5% exhibited FQR. Phylogenetic analysis revealed that 52.5% of E. coli belonged to phylogroup B2, including the high-risk clonal complex (CC)131 CH40-30 (17 isolates) and ST1193 (one isolate). In silico analysis of the ST1193 genome determined O75:H5-B2 (CH14-64), and the carriage of IncI1-I(Alpha) and IncF [F-:A1:B10] plasmids. Notably, core genome single-nucleotide polymorphism (SNP) analysis demonstrated high similarity between the Algerian ST1193 isolate and a previously annotated genome from a hospital in Northwest Spain. Conclusions: This study highlights the spread and genetic diversity of E. coli CC131 CH40-30 and hypervirulent K. pneumoniae clones in Algeria. It represents the first report of a CTX-M-15-carrying E. coli ST1193 in the region. The findings emphasize the urgent need for antibiotic optimization programs and enhanced surveillance to curb the dissemination of high-risk clones that pose an increasing public health threat in Algeria. A simplified method based on virulence traits for E. coli and K. pneumoniae is proposed here for antimicrobial resistance (AMR) monitoring. Full article

(This article belongs to the Special Issue Genomic Analysis of Antimicrobial Drug-Resistant Bacteria)

14 pages, 2600 KiB

Open AccessArticle

Heterogeneity of Biofilm Formation Among Staphylococcus aureus and Coagulase-Negative Staphylococcus Species in Clinically Relevant Intravenous Fat Emulsions

by Gustavo R. Alvira-Arill, Oscar R. Herrera, Jeremy S. Stultz and Brian M. Peters

Antibiotics 2025, 14(5), 484; https://doi.org/10.3390/antibiotics14050484 - 9 May 2025

Abstract

Background: Compared to soybean oil intravenous fat emulsion (SO-IFE), use of mixed-oil IFE (MO-IFE) is associated with reduced rates of catheter-related bloodstream infections caused by coagulase-negative Staphylococcus species (CoNS) in pediatric patients receiving parenteral nutrition. Methods: Using an in vitro biofilm [...] Read more.

Background: Compared to soybean oil intravenous fat emulsion (SO-IFE), use of mixed-oil IFE (MO-IFE) is associated with reduced rates of catheter-related bloodstream infections caused by coagulase-negative Staphylococcus species (CoNS) in pediatric patients receiving parenteral nutrition. Methods: Using an in vitro biofilm model, this study aimed to assess the impact of IFEs on biofilm formation among Staphylococcus species. S. aureus, S. capitis, S. epidermidis, S. haemolyticus, S. hominis, and S. lugdunensis were cultivated as biofilms in media supplemented with SO-IFE, MO-IFE, or fish oil IFE (IFE). Biomass was quantified by the crystal violet method, and follow-up planktonic growth assays assessed antimicrobial effects of IFEs. Results: Compared to SO-IFE, MO-IFE and FO-IFE significantly inhibited biofilm formation of S. aureus but did not impact planktonic growth. Contrary to clinical data, CoNS biofilm formation was not impacted by any of the IFEs tested. S. aureus biofilm inhibition in IFEs was further investigated by comparing differences following growth in SO-IFE supplemented with capric acid, docosahexaenoic acid (DHA), or eicosapenaenoic acid (EPA) to concentrations matching those of MO-IFE. Capric acid supplementation was associated with significant reduction in biofilm formation compared to SO-IFE alone. However, this was attributed to a bactericidal effect based on follow-up planktonic growth assays. Conclusions: These results suggest that biofilm formation in S. aureus is variably impacted by fatty acid composition in clinically relevant IFEs, with capric acid exhibiting bactericidal activity against tested isolates. Full article

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25 pages, 11534 KiB

Open AccessArticle

Repurposing Mouthwashes: Antifungal and Antibiofilm Abilities of Commercially Available Mouthwashes Against Candida spp.

by Marie Maziere, Paulo Rompante, José Carlos Andrade, Beatriz S. F. De Oliveira, Mariana C. Alves and Celia Fortuna Rodrigues

Antibiotics 2025, 14(5), 483; https://doi.org/10.3390/antibiotics14050483 - 9 May 2025

Abstract

Background/Objectives: The main objective was to evaluate and compare the antifungal efficacy against Candida spp. in commercially available mouthwashes distributed in the European market. Indeed, the solution to emerging infectious diseases may no longer lie in costly new drug development but rather [...] Read more.

Background/Objectives: The main objective was to evaluate and compare the antifungal efficacy against Candida spp. in commercially available mouthwashes distributed in the European market. Indeed, the solution to emerging infectious diseases may no longer lie in costly new drug development but rather in unlocking the untapped potential of existing substances. Materials and Methods: Eighteen mouthwashes, chosen based on their composition, were tested in vitro against ten Candida strains, including clinical isolates of oral origin and reference strains, in both planktonic and biofilm forms. The antifungal susceptibility testing was conducted using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) disc diffusion method and the evaluation of the kinetic growth in planktonic Candida. Biofilm reduction was determined by the evaluation of the minimal biofilm eradication concentration (MBEC). Scanning electron microscopy (SEM) analysis was performed to evaluate potential morphological alterations of Candida biofilms. Results: Most mouthwashes effectively reduced biomass production and colony-forming unit (CFU) count. Parodontax Extra showed the highest efficacy. In the disc diffusion assay, Gum Paroex 0.12% exhibited the largest average inhibition zone diameter. Some unusual trends in the data may be explained by a higher reaction of fungal cells and the release of excess biomass during co-incubation in higher concentration of mouthwashes. SEM images revealed significant morphological alterations. Conclusion: Mouthwashes containing chlorhexidine digluconate, either alone or in combination with cetylpyridinium chloride and other active compounds, emerged as a common factor among the most efficacious formulations. In vivo studies will be essential to validate these findings, but mouthwashes may serve as a valuable adjuvant in the treatment of oral candidiasis. Full article

(This article belongs to the Special Issue Microbial Biofilms: Identification, Resistance and Novel Drugs)

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18 pages, 5903 KiB

Open AccessArticle

Prevalence and Antimicrobial Resistance of Listeria monocytogenes Isolated from Dairy Products in Romania

by Filippos Georgios Nikolaou, Liora Mihaela Colobatiu, Laurentiu Mihai Ciupescu, Alexandra Tabaran, Ariana Raluca Hategan, Romolica Mihaiu, Radu Tanasuica, Magdalena Maria Poenaru and Marian Mihaiu

Antibiotics 2025, 14(5), 482; https://doi.org/10.3390/antibiotics14050482 - 9 May 2025

Abstract

Background/Objectives: Listeria monocytogenes is a significant foodborne pathogen associated with dairy products, which can pose serious public health risks, particularly for vulnerable populations. This study aimed to assess the prevalence, serotype distribution, and antimicrobial resistance profiles of Listeria monocytogenes isolated from dairy [...] Read more.

Background/Objectives: Listeria monocytogenes is a significant foodborne pathogen associated with dairy products, which can pose serious public health risks, particularly for vulnerable populations. This study aimed to assess the prevalence, serotype distribution, and antimicrobial resistance profiles of Listeria monocytogenes isolated from dairy products collected in Romania over a three-year period (2021–2023). To the best of our knowledge, this is the first comprehensive study addressing these issues within the country. Methods: A total of 10,306 dairy samples, including milk, cheeses, ice cream, yogurt, and other dairy-based products, were collected and analyzed using standard microbiological methods. Molecular serotyping was performed to identify the most common serogroups. The antimicrobial susceptibility of the isolates was also conducted. Results: The overall prevalence of Listeria monocytogenes was 0.41% (43/10,306). The most frequently detected serogroup was IVb (74.41%), followed by IIa (23.25%) and IIb (2.32%). Ice cream was the most affected product, followed by fresh telemea made from cow milk. Antimicrobial susceptibility testing revealed higher resistance rates for oxacillin and trimethoprim-sulfamethoxazole (13.95% each), while all isolates were susceptible to ciprofloxacin, levofloxacin, and moxifloxacin. Conclusions: The findings emphasize the need for continuous monitoring of Listeria monocytogenes in dairy products, particularly ice cream and fresh cheeses, due to their high contamination rates. The study’s results are valuable for comparative analysis with findings from other countries, helping to establish a broader understanding of Listeria monocytogenes contamination trends and resistance profiles. Full article

(This article belongs to the Special Issue Emerging Challenges in Food Safety: Addressing Antimicrobial Resistance, Virulence Factors, and Biofilm Formation in Food-Borne Pathogens)

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15 pages, 2618 KiB

Open AccessArticle

Pulsed Blue Light and Phage Therapy: A Novel Synergistic Bactericide

by Amit Rimon, Jonathan Belin, Ortal Yerushalmy, Yonatan Eavri, Anatoly Shapochnikov, Shunit Coppenhagen-Glazer, Ronen Hazan and Lilach Gavish

Antibiotics 2025, 14(5), 481; https://doi.org/10.3390/antibiotics14050481 - 9 May 2025

Abstract

Background: Antibiotic-resistant Pseudomonas aeruginosa (P. aeruginosa) strains are an increasing cause of morbidity and mortality. Pulsed blue light (PBL) enhances porphyrin-induced reactive oxygen species and has been clinically shown to be harmless to the skin at low doses. Bacteriophages, viruses that [...] Read more.

Background: Antibiotic-resistant Pseudomonas aeruginosa (P. aeruginosa) strains are an increasing cause of morbidity and mortality. Pulsed blue light (PBL) enhances porphyrin-induced reactive oxygen species and has been clinically shown to be harmless to the skin at low doses. Bacteriophages, viruses that infect bacteria, offer a promising non-antibiotic bactericidal approach. This study investigates the potential synergism between low-dose PBL and phage therapy against P. aeruginosa in planktonic cultures and preformed biofilms. Methods: We conducted a factorial dose–response in vitro study combining P. aeruginosa-specific phages with PBL (457 nm, 33 kHz) on both PA14 and multidrug-resistant PATZ2 strains. After excluding direct PBL effects on phage titer or activity, we assessed effectiveness on planktonic cultures using growth curve analysis, CFU, and PFU. Biofilm efficacy was evaluated using CFU post-sonication, crystal violet staining, and live/dead staining with confocal microscopy. Finally, we assessed reactive oxygen species (ROS) as a potential mechanism using the nitro blue tetrazolium reduction assay. ANOVA or Kruskal–Wallis tests with post hoc Tukey or Conover–Iman tests were used for comparisons (n = 5 biological replicates and technical triplicates). Results: The bacterial growth lag phase was significantly extended for phage alone or PBL alone, with a synergistic effect of up to 144% (p < 0.001 for all), achieving a 9 log CFU/mL reduction at 24 h (p < 0.001). In preformed biofilms, synergistic combinations significantly reduced biofilm biomass and bacterial viability (% Live, median (IQR): Control 80%; Phage 40%; PBL 25%; PBL&Phage 15%, p < 0.001). Mechanistically, PBL triggered transient ROS in planktonic cultures, amplified by phage co-treatment, while a biphasic ROS pattern in biofilms reflected time-dependent synergy. Conclusions: Phage therapy combined with PBL demonstrates a synergistic bactericidal effect against P. aeruginosa in both planktonic cultures and biofilms. Given the strong safety profile of PBL and phages, this approach may lead to a novel, antibiotic-complementary, safe treatment modality for patients suffering from difficult-to-treat antibiotic-resistant infections and biofilm-associated infections. Full article

(This article belongs to the Special Issue Antibiofilm Activity against Multidrug-Resistant Pathogens)

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9 pages, 455 KiB

Open AccessArticle

A Selective Chromogenic Medium for Detecting Meropenem-Resistant Pseudomonas aeruginosa in Respiratory Samples

by Carmen Cintora Mairal, Guillermo Martín-Gutiérrez, Ángel Rodríguez-Villodres, José Miguel Cisneros, José Antonio Lepe and José Manuel Ortiz de la Rosa

Antibiotics 2025, 14(5), 480; https://doi.org/10.3390/antibiotics14050480 - 9 May 2025

Abstract

Background/Objectives: Meropenem is widely used to treat Pseudomonas aeruginosa infections; however, the pathogen’s increasing resistance compromises its efficacy. In this study, we aimed to develop a selective culture medium for detecting the presence of meropenem-resistant Pseudomonas aeruginosa in respiratory specimens within 24 [...] Read more.

Background/Objectives: Meropenem is widely used to treat Pseudomonas aeruginosa infections; however, the pathogen’s increasing resistance compromises its efficacy. In this study, we aimed to develop a selective culture medium for detecting the presence of meropenem-resistant Pseudomonas aeruginosa in respiratory specimens within 24 h. Methods: The medium’s performance was challenged using a collection of 130 clinical Pseudomonas aeruginosa strains (of which 85 were meropenem-susceptible, 14 were meropenem-intermediate, and 21 were meropenem-resistant). Subsequently, clinical validation was carried out using 130 respiratory samples. Results: The selective medium demonstrated excellent sensitivity (average 98.7%) and specificity (average 90%) across bacterial concentrations ranging from 1 × 10⁴ to 1 × 10⁸ CFU/mL, and a high negative predictive value (average 99.2%) compared to the broth microdilution (BMD) method. Clinical validation with bronchoalveolar lavage (BAL) and tracheobronchial aspirate (TBA) clinical specimens (N = 130) revealed a strong performance, with 92,3% categorical agreement. Conclusions: This method accelerates susceptibility testing, is user-friendly, and delivers reliable results, contributing to the optimization of empirical treatment for respiratory tract infections. Full article

(This article belongs to the Special Issue Molecular Epidemiology and Mechanisms of Carbapenem Resistance in Clinical Gram-Negative Bacteria)

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15 pages, 917 KiB

Open AccessArticle

Misconceptions and Behavioral Risks in Parental Antibiotic Use on Romanian Children: A Cross-Sectional Study on Knowledge, Attitudes, and Practices

by Alin Iuhas, Radu Galiș, Marius Rus, Andreea Balmoș, Cristian Marinău, Larisa Niulaș, Zsolt Futaki, Dorina Matioc and Cristian Sava

Antibiotics 2025, 14(5), 479; https://doi.org/10.3390/antibiotics14050479 - 9 May 2025

Abstract

Background: Antimicrobial resistance is a growing global health threat, with antibiotic misuse in pediatric populations being a significant contributing factor. In Romania, antibiotic consumption and resistance rates are among the highest in Europe. Objective: To assess Romanian parents’ knowledge, attitudes, and practices regarding [...] Read more.

Background: Antimicrobial resistance is a growing global health threat, with antibiotic misuse in pediatric populations being a significant contributing factor. In Romania, antibiotic consumption and resistance rates are among the highest in Europe. Objective: To assess Romanian parents’ knowledge, attitudes, and practices regarding antibiotic use in children, and to identify key misconceptions and behavioral risks contributing to inappropriate antibiotic use. Methods: A cross-sectional survey was conducted among 400 parents of hospitalized children in a pediatric department in Romania. Participants completed a 15 item structured questionnaire. Data were analyzed using descriptive statistics, chi-square tests, and binary logistic regression to examine associations and control for potential confounding effects between education level, residential environment, and parental misconceptions regarding antibiotic use. Results: Among the 400 surveyed caregivers, 86% (n = 344) held at least one misconception regarding antibiotic use. Additionally, 42.5% (n = 170) of participants reported that they had never heard of the concept of antibiotic resistance. Misconceptions were significantly more prevalent among individuals with lower levels of education and those residing in rural areas (p < 0.001). While 89.8% (n = 359) stated that they had never administered antibiotics to their children without a physician’s recommendation, a separate subset of 28% (n = 112) acknowledged that they had asked a doctor to prescribe antibiotics for their child. Moreover, 23.3% (n = 93) reported seeking a second medical opinion when antibiotics were not initially prescribed. Conclusions: Despite high adherence to medical advice, widespread misconceptions persist. These findings highlight the need for targeted, population-specific educational interventions to promote rational antibiotic use and address AMR in high-burden settings like Romania. Full article

(This article belongs to the Special Issue Antibiotic Use in the Communities—2nd Edition)

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17 pages, 3081 KiB

Open AccessArticle

Antimicrobial Susceptibility Profiles of Erysipelothrix rhusiopathiae and Riemerella anatipestifer Isolates from Clinical Cases of Waterfowl in Hungary Between 2022 and 2023

by Ádám Kerek, Ábel Szabó and Ákos Jerzsele

Antibiotics 2025, 14(5), 478; https://doi.org/10.3390/antibiotics14050478 - 8 May 2025

Abstract

Background:Riemerella anatipestifer and Erysipelothrix rhusiopathiae remain clinically significant pathogens in the waterfowl industry, causing substantial economic losses and posing potential zoonotic risks. Antimicrobial resistance (AMR) continues to spread in the poultry sector, making regular surveillance of bacterial isolates essential. Methods: In [...] Read more.

Background:Riemerella anatipestifer and Erysipelothrix rhusiopathiae remain clinically significant pathogens in the waterfowl industry, causing substantial economic losses and posing potential zoonotic risks. Antimicrobial resistance (AMR) continues to spread in the poultry sector, making regular surveillance of bacterial isolates essential. Methods: In this study, eight R. anatipestifer and eighteen E. rhusiopathiae strains were isolated from clinical cases in Hungarian waterfowl between 2022 and 2023. Minimum inhibitory concentration (MIC) values were determined for antibiotics of veterinary and public health significance. Results: For R. anatipestifer, high resistance rates were observed for spectinomycin, lincomycin, and tiamulin, while beta-lactam antibiotics (amoxicillin, ceftriaxone, and imipenem) demonstrated strong efficacy. Among the E. rhusiopathiae isolates, resistance to amoxicillin (89%) and enrofloxacin (61%) was notable, whereas ceftriaxone and doxycycline exhibited moderate antibacterial effects. Conclusions: Our findings underscore the importance of targeted antimicrobial use in the waterfowl industry. Beta-lactam antibiotics remain effective, whereas rising resistance to fluoroquinolones and aminoglycosides raise serious concerns. Routine AMR surveillance and the adoption of alternative strategies are crucial for controlling infections and maintaining flock health. Full article

(This article belongs to the Special Issue Virulence, Antimicrobial Resistance and Biofilm Production in Veterinary, Zoonotic and Food-Related Pathogens)

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13 pages, 1585 KiB

Open AccessArticle

Dissemination of Tylosin Residues in the Poultry Environment: Evaluating Litter and Droppings as Sources of Risk

by María Belén Vargas, Ignacia Soto, Francisco Mena, Paula Cortés, Ekaterina Pokrant, Lina Trincado, Matías Maturana, Andrés Flores, Aldo Maddaleno, Lisette Lapierre and Javiera Cornejo

Antibiotics 2025, 14(5), 477; https://doi.org/10.3390/antibiotics14050477 - 8 May 2025

Abstract

Introduction: Tylosin, a veterinary antimicrobial belonging to the macrolide family, is commonly used in the poultry industry. Residues generated from its use can be present in the litter and droppings of treated birds. Due to the diverse uses of poultry byproducts, such as [...] Read more.

Introduction: Tylosin, a veterinary antimicrobial belonging to the macrolide family, is commonly used in the poultry industry. Residues generated from its use can be present in the litter and droppings of treated birds. Due to the diverse uses of poultry byproducts, such as fertilizing agricultural soils or incorporation into the diets of other animal species, there is a risk to public health, as the presence of antimicrobial residues favors the development of antimicrobial resistance, which is a global problem. Objective: This study aimed to evaluate the dissemination of tylosin residues from the litter and droppings of treated birds and untreated birds in a controlled broiler environment. Methods: Bird droppings and litter samples were collected and analyzed using HPLC-MS/MS to detect and quantify tylosin residues. Results: The residue concentrations detected in the dropping matrix only exceeded the Limits of Quantification (LOQ = 4 µg kg⁻¹) in the treated group. The litter matrix had statistically significant differences between the study groups. The persistence of tylosin residues in the litter of birds at day 42 was 290.16 µg kg⁻¹ in the treated group (A) and 9.35 µg kg⁻¹ in the adjacent untreated group (B.1). Conclusions: The results indicate that exposure distance influences tylosin residue dissemination. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

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26 pages, 1252 KiB

Open AccessSystematic Review

Clinical Effectiveness of Penicillin-Free Therapies in First-Line and Rescue Treatments for Helicobacter pylori: A Systematic Review

by Kenza El Boury, Hind Boudarf, Imane Adoud, Soukaina Ouannass, Oussama Abi, Hanane Delsa, Fatima Azzahra Lahlou, Samy Iskandar, Meryem El Jemli, Idrissa Diawara, Mohamed Amine Senhaji, Lhousaine Balouch, Zakaria Belrhiti and Mohamed Kettani Halabi

Antibiotics 2025, 14(5), 476; https://doi.org/10.3390/antibiotics14050476 - 8 May 2025

Abstract

Background and Aims: Amoxicillin is one of the most effective antibiotics for treating Helicobacter pylori infections and is widely used in first-line treatment regimens. However, patients with penicillin allergies cannot receive penicillin-based therapies, which significantly limits effective eradication options. This allergy often compels clinicians [...] Read more.

Background and Aims: Amoxicillin is one of the most effective antibiotics for treating Helicobacter pylori infections and is widely used in first-line treatment regimens. However, patients with penicillin allergies cannot receive penicillin-based therapies, which significantly limits effective eradication options. This allergy often compels clinicians to choose alternative regimens that may be less effective, thereby increasing the risk of treatment failure. Consequently, therapeutic options for these patients are more restricted, and clinicians must carefully select the most appropriate regimen, taking into account both efficacy and the potential for antimicrobial resistance. This review aims to systematically evaluate the efficacy of penicillin-free treatment regimens for the eradication of H. pylori in patients with penicillin allergies. Specifically, it seeks to identify, analyze, and synthesize current clinical evidence to determine the most effective alternative therapies, thereby supporting evidence-based clinical decision-making. Methods: A literature search was conducted using the PubMed and Scopus databases. We began by reviewing the titles and abstracts of all identified studies to determine eligibility. Next, we assessed the full text of potentially eligible articles according to inclusion and exclusion criteria to establish the eligibility of each study. Results: This review included 26 studies comprising 2713 participants, evaluating penicillin-free therapies for H. pylori eradication in penicillin-allergic patients. Key findings demonstrated high eradication rates with bismuth-based quadruple therapies (88–97%), doxycycline-based regimens (86%), and quinolone-based therapies (75–100%), with Sitafloxacin exceeding 90% efficacy. Minocycline-based regimens also showed promising outcomes, with eradication rates between 80% and 85%. Although the PPI–clarithromycin–metronidazole combination was moderately effective, it was less favored as a first-line option. Overall, bismuth-based and quinolone-based therapies emerged as the most effective alternatives. Conclusions: In patients allergic to penicillin, bismuth quadruple therapy has demonstrated an excellent rate of eradication. Quinolone-based regimens are emerging as a promising alternative in first-line treatment or in cases of treatment failure. Vonoprazan-based therapy is an effective regimen. Combined with clarithromycin and metronidazole, vonoprazan enhances eradication rates and demonstrates effectiveness, including in clarithromycin-resistant strains. Full article

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16 pages, 3095 KiB

Open AccessArticle

High Prevalence of Cefiderocol Resistance Among New Delhi Metallo-β-Lactamase Producing Klebsiella pneumoniae High-Risk Clones in Hungary

by Lilla Buzgó, Zsanett Kiss, Dániel Göbhardter, Virág Lesinszki, Erika Ungvári, Zoltán Rádai, Levente Laczkó, Ivelina Damjanova, Gábor Kardos and Ákos Tóth

Antibiotics 2025, 14(5), 475; https://doi.org/10.3390/antibiotics14050475 - 8 May 2025

Abstract

Background/Objectives: The global spread of carbapenemase-producing K. pneumoniae (CPKP) strains represent a severe public health threat due to very limited choice of antibacterial therapy. Cefiderocol, a novel siderophore-cephalosporin, may represent a new therapeutic option but resistance is increasingly being described. Our aim was [...] Read more.

Background/Objectives: The global spread of carbapenemase-producing K. pneumoniae (CPKP) strains represent a severe public health threat due to very limited choice of antibacterial therapy. Cefiderocol, a novel siderophore-cephalosporin, may represent a new therapeutic option but resistance is increasingly being described. Our aim was to investigate in vitro cefiderocol susceptibility among CPKP strains in Hungary and assess correlations between resistance, carbapenemase types, and clonal lineages. Methods: The study was performed on 420 CPKP strains from 34 Hungarian healthcare institutes (HCIs) submitted to the National Reference Laboratory of Antimicrobial Resistance (March 2021 to April 2023). The disk diffusion method (Liofilchem, Via Scozia, Italy) was used for in vitro cefiderocol susceptibility testing (according to EUCAST guidelines). For molecular epidemiologic investigation, we used whole genome sequencing (Illumina MiSeq, 150 bp paired-end) and pulsed-field gel electrophoresis (PFGE). Carbapenemase gene type was determined by multiplex PCR. Statistical analysis was performed in R (v.4.2.0). Results: Dominant high-risk clones (ST147, ST395, ST258) exhibited regional distribution, with ST147/NDM-1 strains showing the highest cefiderocol resistance (75%). Overall resistance was 65%. Carbapenemase gene types occurred as follows: 35 bla_VIM, 53 bla_KPC, 57 bla_OXA-48-like, 153 bla_NDM, and 122 bla_OXA-48-like+bla_NDM. Cefiderocol resistance rates by carbapenemase type were 20%, 44%, 70%, and 75% in the case of bla_VIM, bla_OXA-48-like, bla_KPC, bla_NDM, and bla_OXA-48-like+bla_NDM. Conclusions: The results show a high prevalence of cefiderocol resistance in CPKP in Hungary, with different rates of resistance in different carbapenemase gene-carrying high-risk clones, highlighting the growing challenge in treating these infections. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

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